Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales

Atherosclerosis. 2015 May;240(1):190-6. doi: 10.1016/j.atherosclerosis.2015.03.003. Epub 2015 Mar 6.

Abstract

Background/objective: Familial Hypercholesterolaemia (FH) is caused by mutations in genes of the Low Density Lipoprotein (LDL) receptor pathway. A definitive diagnosis of FH can be made by the demonstration of a pathogenic mutation. The Wales FH service has developed scoring criteria to guide selection of patients for DNA testing, for those referred to clinics with hypercholesterolaemia. The criteria are based on a modification of the Dutch Lipid Clinic scoring criteria and utilise a combination of lipid values, physical signs, personal and family history of premature cardiovascular disease. They are intended to provide clinical guidance and enable resources to be targeted in a cost effective manner.

Methods: 623 patients who presented to lipid clinics across Wales had DNA testing following application of these criteria.

Results: The proportion of patients with a pathogenic mutation ranged from 4% in those scoring 5 or less up to 85% in those scoring 15 or more. LDL-cholesterol was the strongest discriminatory factor. Scores gained from physical signs, family history, coronary heart disease, and triglycerides also showed a gradient in mutation pick-up rate according to the score.

Conclusion: These criteria provide a useful tool to guide selection of patients for DNA testing when applied by health professionals who have clinical experience of FH.

Keywords: Cholesterol; Criteria; Diagnosis; Familial Hypercholesterolaemia; Genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticholesteremic Agents / therapeutic use
  • Apolipoprotein B-100 / genetics*
  • Biomarkers / blood
  • Cholesterol, LDL / blood
  • DNA Mutational Analysis*
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Humans
  • Hyperlipidemia, Familial Combined / blood
  • Hyperlipidemia, Familial Combined / diagnosis
  • Hyperlipidemia, Familial Combined / drug therapy
  • Hyperlipidemia, Familial Combined / epidemiology
  • Hyperlipidemia, Familial Combined / genetics*
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / diagnosis
  • Hyperlipoproteinemia Type II / drug therapy
  • Hyperlipoproteinemia Type II / epidemiology
  • Hyperlipoproteinemia Type II / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Patient Selection
  • Pedigree
  • Phenotype
  • Predictive Value of Tests
  • Proprotein Convertase 9
  • Proprotein Convertases / genetics*
  • Receptors, LDL / genetics*
  • Risk Assessment
  • Risk Factors
  • Serine Endopeptidases / genetics*
  • Triglycerides / blood
  • Wales / epidemiology

Substances

  • APOB protein, human
  • Anticholesteremic Agents
  • Apolipoprotein B-100
  • Biomarkers
  • Cholesterol, LDL
  • Genetic Markers
  • LDLR protein, human
  • Receptors, LDL
  • Triglycerides
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases